# US 10,765,745 B2 · Multifunctional nanoparticle systems and methods for cancer diagnosis and combination therapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,765,745 B2 - Document ID: US10765745B2 - Status: Granted - Kind: B2 - Application number: 15/260,835 - Filed: 2016-09-09 - Published: 2017-03-09 - Granted: 2020-09-08 - Earliest claimed: 2015-09-09 - Assignees: Board of Regents, The University of Texas System - Applicants: Board of Regents, the University of Texas System - Inventors: Kytai Nguyen; Jyothi Menon; Debabrata Saha - Web page: https://patentgrep.com/patent/US10765745B2 ## CPC - A61K 41/0038: {Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10)} - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid - A61K 33/243: Platinum; Compounds thereof - A61K 33/244: Lanthanides; Compounds thereof (medicinal preparations containing radioactive lanthanides for use in therapy or testing in vivo A61K51/00) - A61K 47/551: {one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid} - A61K 47/6937: {the polymer being PLGA, PLA or polyglycolic acid} - A61K 49/1857: {the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA} - A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)} - A61K 9/5169: {Proteins, e.g. albumin, gelatin} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract In one aspect, compositions comprising a population of core-shell nanoparticles are described herein. In some cases, the population of core-shell nanoparticles comprises a core component and a shell component encapsulating or surrounding the core component. Additionally, one or more radiosensitizers are disposed in or dispersed throughout the core component, or an interior region of the core component. Similarly, one or more chemotherapeutic agents are disposed in or dispersed throughout the shell component, or an interior region of the shell component. Moreover, in some cases, the core component is formed from one or more biodegradable polymers. Further, in some instances, the shell component is formed from one or more stimuli responsive polymers, such as a temperature-responsive polymer and/or pH-responsive polymer. ## Claims ### Claim 1 A method of diagnosing and/or treating a cancer; the method comprising: administering to a patient in need thereof a population of core-shell nanoparticles, the core-shell nanoparticles comprising: a core component; a shell component encapsulating the core component; one or more radiosensitizers disposed in the core component; and one or more chemotherapeutic agents disposed in the shell component, wherein the core component is formed from one or more biodegradable polymers; and wherein the shell component is formed from one or more stimuli responsive polymers that undergo a reversible phase transition in response to an external stimulus; exposing the core-shell nanoparticles to the external stimulus; releasing a portion of the chemotherapeutic agents in a burst release from the shell component in response to the exposure to the external stimulus; and releasing a portion of the radiosensitizers in a sustained release from the core component in response to the exposure to the external stimulus. ### Claim 2 (depends on 1) The method of claim 1, wherein the core component is formed from a gelatin, chitosan, alginate, starch, polysaccharide, cellulose or cellulose derivative, dextrin, dextran, fibrin, fibrinogen, fibronectin, collagen, elastin, laminin, glycosaminoglycan, hyalauronic acid, albumin, polypeptide, polylactic acid (PLA), polyglycolic acid (PGA), polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), polyglycolide, polyanhydride, polyphosphazene, polyurethane, PLGA-chitosan copolymer, PLGA-PEG (polyethylene glycol) copolymer, or a mixture or combination thereof. ### Claim 3 (depends on 2) The method of claim 2, wherein the core component is formed from PLGA. ### Claim 4 (depends on 1) The method of claim 1, wherein the shell component is temperature-responsive. ### Claim 5 (depends on 1) The method of claim 1, wherein the shell component is pH responsive. ### Claim 6 (depends on 1) The method of claim 1, wherein the shell component is formed from a copolymer of a temperature-responsive first polymer and a pH-responsive second polymer, wherein the first and second polymers differ. ### Claim 7 (depends on 6) The method of claim 6, wherein the shell component is formed from a poly(N-isopropylacrylamide) (PNIPAAm)-carboxymethyl chitosan (CMC) copolymer. ### Claim 8 (depends on 1) The method of claim 1, wherein the core-shell nanoparticles further comprise a magnetic resonance imaging (MRI) contrast agent or a computed tomography (CT) contrast agent disposed in the core component and/or the shell component. ### Claim 9 (depends on 8) The method of claim 8, wherein the contrast agent comprises superparamagnetic iron oxide (SPIO) or a lanthanide ion. ### Claim 10 (depends on 1) The method of claim 1, wherein the composition further comprises an imaging agent disposed in the core component and/or the shell component. ### Claim 11 (depends on 10) The method of claim 10, wherein the imaging agent comprises an organic dye, luminescent biomolecule, or a semiconductor nanocrystal. ### Claim 12 (depends on 1) The method of claim 1, wherein the core-shell nanoparticles further comprise a targeting agent attached to the outer surface of the core-shell nanoparticles. ### Claim 13 (depends on 12) The method of claim 12, wherein the targeting agent comprises folic acid. ### Claim 14 (depends on 1) The method of claim 1, wherein the population of core-shell nanoparticles has an average diameter of 300 nm or less. ### Claim 15 (depends on 1) The method of claim 1, wherein the population of core-shell nanoparticles has a negative zeta potential. ### Claim 16 (depends on 15) The method of claim 15, wherein the negative zeta potential has an absolute value of 10 mV or more. ### Claim 17 (depends on 16) The method of claim 16, wherein the negative zeta potential has an absolute value of 10-40 mV. ### Claim 18 (depends on 1) The method of claim 1, wherein releasing the portion of the chemotherapeutic agents and releasing the portion of the radiosensitizers begin simultaneously. ### Claim 19 A method of diagnosing and/or treating a cancer, the method comprising: administering to a patient in need thereof a population of core-shell nanoparticles, the core-shell nanoparticles comprising: a core component; a shell component encapsulating the core component; one or more radiosensitizers disposed in the core component; and one or more chemotherapeutic agents disposed in the shell component, wherein the core component is formed from one or more biodegradable polymers; and wherein the shell component is formed from one or more stimuli responsive polymers that undergo a reversible phase transition in response to an external stimulus; exposing the core-shell nanoparticles to the external stimulus, releasing a portion of the chemotherapeutic agents in a burst release from the shell component in response to the exposure to the external stimulus; and releasing a portion of the radiosensitizers in a sustained release from the core component in response to the exposure to the external stimulus, wherein the composition is administered to the patient as an aerosol or an inhalant via a nebulizer and wherein the cancer is lung cancer. ### Claim 20 (depends on 1) The method of claim 1, wherein the radiosensitizers, chemotherapeutic agents, or both are releasable from the core-shell nanoparticles in the presence of the external stimulus and are unreleasable in the absence of the external stimulus. ### Claim 21 (depends on 1) The method of claim 1, wherein the burst release corresponds to a release of at least 20% of the chemotherapeutic agents within a period of 2 days or less. ### Claim 22 (depends on 1) The method of claim 1, wherein the sustained release corresponds to a release of less than 20% of the radiosensitizers within 2 days. ### Claim 23 (depends on 1) The method of claim 1, wherein the external stimuli comprises radiation therapy. ### Claim 24 (depends on 23) The method of claim 23, wherein the radiation therapy comprises external beam radiation therapy, brachytherapy, or systemic radioisotope therapy. ### Claim 25 (depends on 1) The method of claim 1, wherein the external stimuli comprises an applied external magnetic field. ### Claim 26 (depends on 5) The method of claim 5, wherein the pH-responsive shell material is a pH-responsive polymer.